Giant axonal neuropathy: A rare disease hidden in polyneuropathy

Abstract

Background& Objective: Giant axonal neuropathy (GAN) is a serious progressive neurodegenerative disease. The aim of this study is to evaluate the frequency and phenotypic-genotypic characteristics of GAN patients, which, like many rare diseases, is disguised under the name of polyneuropathy, and to present our experience.

Methods: In this retrospective observational study, 105 pediatric patients with polyneuropathy were screened. Demographic characteristics and clinical diagnoses were reviewed. The mean age of the patients was 10.9 years (2-18), 59 were boys (56%) and 46 were girls (44%). GAN patients who were genetically diagnosed by single gene analysis were clinically evaluated in detail.

Results: Regarding the etiology of polyneuropathy, 43% of patients had acquired and 57% had hereditary causes. Among hereditary cases, 29% had an unknown diagnosis, and 5% were diagnosed with GAN, presenting first with gait disturbance. These patients exhibited axonal sensorimotor polyneuropathy and diverse hair types (20% straight, 20% kinky, 40% curly, 20% slightly curly). Findings included carious teeth (40%), hyperplexia (20%), and apnea (20%). Disease progression included worsening scoliosis and limb deformities (pes cavus), with pathological cranial MRI findings. Literature identified 5 GAN patients with a homozygous deletion of GAN gene exon 2-5, classified as likely pathogenic (Class 4).

Conclusion: This study highlights the frequency of GAN among undiagnosed polyneuropathies in childhood. Although the phenotype-genotype correlation for giant axonal neuropathy has not yet been determined, we hope that further studies in the field of molecular biology will increase the chances of a better quality of life.